Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Claims 13-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/2/2025.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3-5 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 3 recites the language “wherein between elution steps, the construct is subjected to processes including drying, transport, sequestration in radiation proof containers, delivery to end users of the daughter isotope, and combinations thereof.” The claim language is indefinite since a claim that recites a list of alternatives should be a closed grouping. See MPEP 2173.05(h). I. Here, it is unclear what other alternative “processes” are intended to be encompassed by the claim.
Claim 4 recites the limitation "the fluid" in line 1. There is insufficient antecedent basis for this limitation in the claim. For purposes of compact prosecution, the fluid is interpreted as referring to the eluent used for eluting.
Claim 5 recites the limitation “wherein the parent isotope displays a radioactivity that does not decrease as a result of subsequent elutions” which lacks clarity since elution or “milking” removes accumulated daughter isotope and equilibration necessarily reduces the parent isotope activity since it decays to accumulate more daughter isotope. Parent isotope radioactivity must always be decreasing as a result of decay. For purposes of compact prosecution, the claim limitation is interpreted as referring to the parent isotope remaining on the resin as a result of subsequent elutions. Support for this interpretation is in the Specification as filed at [52]).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 4-6, and 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Czerwinski et al (US 2022/0339292).
First, “equilibrate” in claim 1 is broadly interpreted as referring to allowing some amount of daughter isotope to build up and not any particular amount or fully saturated amount or secular equilibrium. Support for this interpretation is in the Specification as filed at [36] where equilibration time is less than less than full saturation.
Czerwinski discloses a method for generating Ac and Ra (i.e., a daughter isotope), the method comprising:
Contacting a solution including Th with a titania ion exchange column to produce a Th-loaded titania material (i.e., contacting an inorganic metal oxide ion exchange column with parent isotope to create a column-parent isotope construct);
Eluting the Th-loaded material with a wash solution to produce an eluted solution containing eluted compounds including Ac and Ra (i.e., Eluting the daughter isotope from the column); (see [0027] and [0035-0039]).
Where eluting/milking is performed periodically on a schedule or at random intervals based on Ac need (i.e., Repeating step b) (see [0039].
Regarding allowing the column to equilibrate between parent and daughter isotopes, Czerwinski discloses a method where daughter isotopes are allowed to build up from the parent isotope decay and where the generator is milked periodically or at random intervals (see [0039]). It would have been obvious to one of ordinary skill in the art at the time of filing of the invention to perform the method for generating as disclosed by Czerwinski where in order to milk the generator periodically or intermittently, daughter isotopes are allowed to build up (i.e., equilibrate between parent and daughter isotopes) between elution steps otherwise there would be insufficient daughter isotopes to elute.
Regarding claim 2, Czerwinski discloses a method where the parent is thorium and the daughter isotope is Ra (see [0065]). Czerwinski further discloses that a sufficient amount of Ra can be built up over a reasonable time frame of 3-4 weeks (see [0065]). It would have been obvious to one of ordinary skill in the art at the time of filing of the invention to perform the method as disclosed by Czerwinski where the equilibrate period is 3-4 weeks when Ra is the desired isotope since Czerwinski discloses that a sufficient amount of RA can be built up in the generator in 3-4 weeks.
Regarding claim 4, Czerwinski discloses a method where the daughter isotope is eluted with acetic acid (HOA)/sodium acetate (NaOA) solution (see [0039]).
Regarding claim 5, Czerwinski discloses a method where there is less than 0.001% of Th loss after elution (see [0100]).
Regarding claim 6, Czerwinski discloses a method comprising a pure titania (see [0067]).
Regarding claim 9, Czerwinski discloses a method where the parent isotope is 229Th and the daughter isotopes are 225Ac and 225Ra (see [0030]).
Regarding claim 10, Czerwinski discloses a method where the daughter isotope is eluted with acetic acid (HOA)/sodium acetate (NaOA) solution (see [0039]).
Regarding claim 11, Czerwinski discloses a method where the eluent is a solution having a pH of 4 (see [0083]).
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Czerwinski as applied to claim 1, and in further view of Quirico et al (US 8,708,352).
As applied to claim 1, Czerwinski discloses a method for generating daughter isotopes, the method comprising contacting a titania ion exchange column with a thorium parent isotope to create a column-parent isotope construct, allowing the column to equilibrate between the parent and daughter isotopes; eluting the daughter isotopes from the column; and repeating steps b and c.
Czerwinski does not a method comprising in between elution steps, subjecting the construct to processes including drying, transport, sequestration in radiation proof containers, delivery to end users of the daughter isotope, and combinations thereof.
Quirico discloses an infusion system comprising a shielding assembly comprising a compartment for containing a radionuclide generator (see Col 6, Ln 60-67), the system comprising wheels to make the system mobile (see Col 3, LN 37-39), and a method of operation wherein after the elution process for patent infusion the system can be moved to a new site if the generator is not depleted (see Col 16, Ln 1-2). It would have been obvious to one of ordinary skill in the art at the time of filing of the invention to perform a method as disclosed by Czerwinski where the construct is subjected to transport to a new site after elution as disclosed by Quirico so that the generator can be used if the generator is not depleted as suggested by Quirico.
Claims 7 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Czerwinski as applied to claim 1 and in further view of Paris et al (US 2018/0233243).
As applied to claim 1, Czerwinski discloses a method for generating daughter isotopes, the method comprising contacting a titania ion exchange column with a thorium parent isotope to create a column-parent isotope construct, allowing the column to equilibrate between the parent and daughter isotopes; eluting the daughter isotopes from the column; and repeating steps b and c.
Regarding claim 7, Czerwinski discloses that the method may be implemented in many manners (see [0209]). Czerwinski discloses a method comprising periodically harvesting Radium-224 from the decay of Thorium-228 [0097]. Czerwinski further discloses a method where the column is allowed to stand for 3-4 weeks to allow Radium-224 to build up from Thorium-228 decay (see [0097]).
Czerwinski does not specifically disclose a method the equilibration step having a duration between 5 and 14 days.
Paris discloses a method for generating daughter isotopes in a radioisotope generator having a stationary phase comprising titanium oxide (see [0001]). Paris discloses a method where parent isotope is initially loaded on the stationary phase and the daughter radioisotope is continuously produced by the disintegration of the parent isotope for use in nuclear medicine, biomedical research and diagnostic (see [0015] to [0019]). Paris discloses eluting the daughter radioisotope when the amount of daughter radioisotope is estimated to be sufficient (see [0019]). Paris therefore suggests that the time before elution of a column-parent isotope construct (i.e., the equilibration step) is a results-effective variable on the amount of daughter isotope eluted and that the amount of daughter isotope.
It is well established that optimization within prior art conditions or through routine experimentation in the pertinent art are unpatentable as obvious if a person of ordinary skill in the art has a motivation to optimize and a reasonable expectation of success. Here, a person of ordinary skill in the art would be motivated to provide for a sufficient equilibration time to produce sufficient daughter isotope for the end-use and would also have a reasonable expectation of success because Paris suggests that the amount of daughter isotope required is an estimable amount. Czerwinski also discloses a method where the daughter radionuclides are used as radiotherapeutic agents in the treatment of malignancies (see [0002]) and where eluting is performed at intervals depending on need (see [0039]). It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to improve upon the equilibrate step of 3-4 weeks as disclosed by Czerwinski to determine optimum or workable range including a claimed range of 5 to 14 days as a matter of routine optimization for constant amounts of Radium-224 needed for the specific nuclear medical use or research and diagnostic.
Regarding claim 12, Czerwinski does not disclose a method wherein the equilibration step has a duration to allow for daughter isotope saturation rates of between 1 percent and 50 percent. It would have been prima facie obvious to one of ordinary skill in the art at the time of the invention to improve upon the equilibrate step of 3-4 weeks as disclosed by Czerwinski to determine optimum or workable duration including a claimed duration to allow for daughter isotope saturation rates of between 1 percent and 50 percent as a matter of routine optimization for constant amounts of Radium-224 required for the specific nuclear medical use or research and diagnostic.
Claims 8 is rejected under 35 U.S.C. 103 as being unpatentable over Czerwinski as applied to claim 1 and in further view of Shanks et al (US 2012/0285294)
As applied to claim 1, Czerwinski discloses a method for generating daughter isotopes, the method comprising contacting a titania ion exchange column with a thorium parent isotope to create a column-parent isotope construct, allowing the column to equilibrate between the parent and daughter isotopes; eluting the daughter isotopes from the column; and repeating steps b and c.
Regarding claim 12, Czerwinski does not specifically disclose a method the equilibration step is selected based on decay rates of the parent isotope and daughter isotope.
Shanks discloses a multiple generator elution system comprising forming an elution schedule based on using calculations taking into account parent nuclide half-life and decay equation and the daughter nuclide half-life and decay equation (see [0039]). Shanks discloses a system achieving workflow efficiencies and matching demand with supply (see [0031]). It would have been obvious to one of ordinary skill in the art at the time of filing of the invention perform the method for generating isotopes as disclosed by Czerwinski and to set the equilibrate step and elution (i.e., elution schedule) and use the parent and daughter isotope half-life and decay equation (decay rates) as disclosed by Shanks, in order to form workflow efficiencies and match the demand with the supply of daughter isotopes.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL FORREST whose telephone number is (571)270-5833. The examiner can normally be reached Monday-Friday (10AM-6PM).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sally A Merkling can be reached at (571)272-6297. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/MICHAEL FORREST/Primary Examiner, Art Unit 1738